Various drugs including natural products, protein or peptide anticancer drugs, and chemically synthetic anticancer drugs, have been developed and used so far. However, most of these drugs cause serious side effects affecting normal cells in vivo, and may not work depending on the type of carcinoma. In general cases, the drugs may also not work depending on patients suffering from the same type of carcinoma. Under such circumstances, numerous world-wide studies have been conducted to develop, as novel anticancer drugs used to solve these problems, anticancer drugs capable of selectively removing only cancer cells without affecting normal cells in vivo and further removing all types of cancer cells as well.
A transcription factor CP2c (also known as the terms CP2, Tfcp2, LSF, LBP1, UBP1, etc.) is widely expressed in various mammals, and the activity of CP2c is elaborately regulated as the cells transition from the resting phase (GO) to the DNA replication phase (S), the process of which is essential in allowing the cells to pass through the G1/S transition phase. The regulation of CP2c activity is mostly achieved through post-translational modifications, and a low level of the CP2c activity is maintained constantly. However, because the CP2c is overexpressed in tumor cells, it plays a critical role in carcinogenesis.
In this regard, a research group at Boston University (USA) reported Factor Quinolinone Inhibitor 1 (FQI1) as a compound for inhibiting the cellular activity of CP2c in a liver cancer cell line, identified FQI1 and derivatives thereof using a chemical library screening method, and found that the FQI1 and derivatives thereof are successful in inhibiting only the cancer cells without exerting any influence on normal cells in cell and mouse xenograft models (Grant et al., Antiproliferative small-molecule inhibitors of transcription factor LSF reveal oncogene addiction to LSF in hepatocellular carcinoma, Proc. Natl. Acad. Sci. 2012; 109(12): 4503-4508).
Further, the present inventors also have reported four novel peptide motifs (HXPR, PHL, ASR, and PXHXH) recognizing a specific region of CP2c (Kang et al., Identification and characterization of four novel peptide motifs that recognize distinct regions of the transcription factor CP2, FEBS Journal 2005; 272:1265-1277), and proposed that the CP2c recognizes specific binding motifs of a target protein and interacts with the protein to regulate various cellular activities. In their follow-up study, the present inventors have screened peptides inhibiting the binding of CP2c to DNA by means of an in vitro analysis method based on a DNA immunoprecipitation assay that is useful for analyzing DNA-protein interactions with very specific and high sensitivity, and thus found that Peptide 5 composed of 12 amino acids inhibits CP2c-DNA binding in a concentration-dependent manner (Kim et al., A DNA immunoprecipitation assay used in quantitative detection of in vitro DNA-protein complex binding, Analytical Biochemistry. 2013; 441: 147-151).